Recommended Dosage and Treatment Approach for Ibsrela (Tenapanor) in IBS-C
The recommended dosage of Ibsrela (tenapanor) for adults with constipation-predominant irritable bowel syndrome (IBS-C) is 50 mg orally twice daily, taken immediately prior to breakfast and dinner. 1
Dosing and Administration Details
- Timing: Take Ibsrela immediately before breakfast (or first meal of the day) and immediately before dinner 1
- Missed dose management: If a dose is missed, skip it and take the next dose at the regular time; do not double up doses 1
- Duration: Tenapanor has been studied for treatment periods up to 52 weeks with maintained efficacy and tolerability 2
Mechanism of Action
Tenapanor is a first-in-class, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3 (NHE3), which:
- Is expressed on the apical surface of the small intestine and colon
- Is primarily responsible for sodium absorption in the intestine
- When inhibited, decreases absorption of sodium and phosphate
- Increases water secretion into the intestinal lumen
- Has demonstrated antinociceptive effects 3
Efficacy
Tenapanor has demonstrated significant efficacy in multiple clinical trials:
- 34.1% of tenapanor-treated patients met the FDA responder endpoint for IBS-C versus 21.7% in placebo groups 3
- Showed higher success rates compared to placebo for:
- Abdominal pain improvement (risk difference: 12.1%)
- Complete spontaneous bowel movement (CSBM) response (risk difference: 11.3%)
- Adequate relief of IBS symptoms at 12 weeks (58.1% vs 41.1%) 3
- In the T3MPO-2 trial (26-week study), 36.5% of tenapanor-treated patients were combined responders versus 23.7% with placebo (p<0.001) 4
Adverse Events and Safety Monitoring
- Most common adverse event: Diarrhea (14.8% with tenapanor vs 2.3% with placebo) 3
- Discontinuation rate due to diarrhea: 6.5-6.6% of patients receiving tenapanor 3, 4
- Severity of diarrhea: Typically mild to moderate and transient 4
- Management of severe diarrhea: If severe diarrhea occurs, suspend dosing and rehydrate the patient 1
- Long-term safety: Similar safety profile maintained over ≥52 weeks of treatment 2
Important Contraindications and Warnings
- Absolute contraindications:
- Patients less than 6 years of age due to risk of serious dehydration
- Patients with known or suspected mechanical gastrointestinal obstruction 1
- Caution/avoidance:
- Avoid use in patients 6 years to less than 12 years of age
- Not established for use in patients less than 18 years of age 1
Treatment Algorithm for IBS-C
First-line approaches (try before considering tenapanor):
- Lifestyle modifications
- Dietary changes (soluble fiber, low FODMAP diet)
- Over-the-counter laxatives
When to initiate tenapanor:
- For patients with inadequate response to first-line treatments
- When both abdominal pain and constipation are significant symptoms
Monitoring after initiation:
- Assess for diarrhea, especially within first few weeks
- Evaluate symptom improvement at 4-12 weeks
- Continue treatment if beneficial with periodic reassessment
Drug Interactions
- OATP2B1 substrates: Potential for reduced exposure of concomitant drugs (e.g., enalapril)
- Monitoring: Watch for signs related to loss of efficacy of concomitantly administered drugs
- Management: Adjust dosage of concomitant drugs as needed 1
Clinical Advantages
- Minimal systemic absorption: Tenapanor is locally acting and minimally absorbed, reducing systemic side effects 5
- Hydro-electrolyte balance: Despite increased fecal sodium and water excretion, tenapanor does not appear to cause significant short- or long-term hydro-electrolyte imbalances 5
- Novel mechanism: Offers an alternative approach for patients who have failed other treatments 6
Tenapanor represents a valuable addition to the treatment arsenal for IBS-C, with demonstrated efficacy for both abdominal pain and constipation symptoms, and a generally manageable safety profile when used as directed.